Description: This proposal requests renewal for 3 years of a collaborative agreement between NIMH and extramural site at Columbia, Harvard, and Washington Universities to collect diagnostic information and DNA on individuals in pedigrees containing two or more schizophrenics. We propose to complete the extension of 108 pedigrees and to ascertain an additional 54 multiplex schizophrenia pedigrees, thereby providing information on about 400 schizophrenics and 950 non- schizophrenics in 162 pedigrees. This includes information on about 450 individuals in 54 families at each of the three collaborating sites. These pedigrees are systematically ascertained through two core schizophrenic and extended according to explicit rules.They will contain about 200 pairs of schizophrenic siblings. Simulation studies of power to detect linkage and amount of linkage information in the proposed sample indicate the feasibility of detecting linkage and mapping susceptibility loci if 25 percent or more of the cases of schizophrenia are attributable to variation in a single gene or a small number of epistatically interacting loci.